|Year : 2019 | Volume
| Issue : 2 | Page : 138-141
First report of glycogen storage disease type 111a in a Nigerian child
Idowu O Senbanjo1, Moriam O Lamina2, Tolulope Kumolu-Johnson2, Hala El-Said3, Mohamed Abdel Salam El-Guindi4
1 Department of Paediatrics and Child Health, Lagos State University College of Medicine, Lagos, Nigeria
2 Department of Paediatrics and Child Health, Lagos State University Teaching Hospital, Lagos, Nigeria
3 Department of Clinical Biochemistry, National Liver Institute, Menoufia University, Menoufia, Egypt
4 Department of Paediatrics, National Liver Institute, Menoufia University, Menoufia, Egypt
|Date of Web Publication||10-Jun-2019|
Dr. Idowu O Senbanjo
Department of Paediatrics and Child Health, Paediatrics Gastroenterology/Hepatology/Nutrition Unit, Lagos State University College of Medicine, PMB 21266, Ikeja, Lagos
Source of Support: None, Conflict of Interest: None
Glycogen storage disease (GSD) is a rare inborn error of metabolism with an incidence of 1/20,000–40,000 live births. Some of the presenting clinical features can mimic diseases commonly seen in the tropics and subtropics. We report a 14-month-old Nigerian child who presented at our institution with GSD Type 111a to alert physicians on the need to consider and recognise this rare disorder. The child presented with progressive abdominal swelling due to marked hepatomegaly. From the clinical history, the only clue to hypoglycaemia was that she eats very frequently. Her random blood sugar was normal; however, fasting blood sugar was low. The diagnosis was further entertained with laboratory results showing hypercholesterolaemia and uricaemia and confirmed by histology of biopsied liver tissue. GSD should be suspected in a child with unexplained hepatomegaly and investigated accordingly.
Keywords: Glycogen storage disease, child, Nigeria
|How to cite this article:|
Senbanjo IO, Lamina MO, Kumolu-Johnson T, El-Said H, El-Guindi MA. First report of glycogen storage disease type 111a in a Nigerian child. Niger Postgrad Med J 2019;26:138-41
|How to cite this URL:|
Senbanjo IO, Lamina MO, Kumolu-Johnson T, El-Said H, El-Guindi MA. First report of glycogen storage disease type 111a in a Nigerian child. Niger Postgrad Med J [serial online] 2019 [cited 2019 Aug 22];26:138-41. Available from: http://www.npmj.org/text.asp?2019/26/2/138/259910
| Introduction|| |
Glycogen storage disease (GSD) is a group of diseases due to inborn metabolic defects of glycogen synthesis or breakdown within muscles, liver and other cell types., The overall estimated incidence of GSD ranges between one in every 20,000–40,000 live births. Based on the different enzyme defects, there are over 12 types of GSD reported in the literature. Each disorder has a different enzyme lack or malfunction.
GSD Type 111 is inherited as an autosomal recessive disorder. It is also known as Cori's or Forbes disease in honour of scientists that describe the features of the disorder. GSD Type III is due to deficiency of glycogen-debranching enzyme, amylo-1,6-glucosidase, which results in incomplete degradation of the glycogen molecule. In GSD Type III, when the enzyme deficiency involves both the liver and muscle, it is called GSD Type IIIa and when it is limited to the liver alone, it is referred to as GSD Type IIIb. The frequency of occurrence of GSD Type III is relatively high among Sephardic Jews of North African extraction and Faroese populations of Faroe Islands., A recent study also suggests relatively high incidence among Inuit children from Quebec, Canada. The clinical presentation in children with GSD includes hypoglycaemia, growth retardation and hepatomegaly. These clinical features are also commonly associated with disease condition such as protein-energy malnutrition and infectious diseases which abound in the tropics and subtropics.
The definitive diagnosis of GSD relies on histology of biopsied liver tissue and genetic test. On light microscopy, histopathology of liver biopsy specimen shows inflammatory changes with great elevation of abnormal-structured glycogen content, while molecular genetic testing through full gene sequencing shows a gene change in the area associated with GSD IIIa. The gene responsible for making debranching enzyme is called amylo-1, 6-glucosidase, 4-alpha-glucoanotransferase gene. To the best of our knowledge, there are no published cases of GSD in Nigerian children. Therefore, we described a case of GSD Type 111a in a Nigerian girl to alert physicians on the need to consider and recognise this rare disorder.
| Case Report|| |
A 14-month-old female child was referred to the paediatric gastroenterology clinic at the Lagos State University Teaching Hospital, Ikeja on 11th January 2016 with a history of abdominal swelling of about 3 weeks before presentation. She also had a fever of 2 weeks. Abdominal swelling was generalised and progressively increased in size with associated laboured breathing but no swelling in any other part of the body. There was no vomiting, change in bowel habit, jaundice, no passage of dark-coloured urine or pale-coloured stools. There was also no significant history of weight loss or cough. Fever which was high grade had resolved before presentation following the use of parenteral antibiotics prescribed and administered at a private hospital. There was no associated convulsion, excessive sweating or the loss of consciousness. Examination and investigations done at the private hospital which included abdominal ultrasound [Figure 1] and abdominal computed tomography scan showed marked hepatomegaly, hence the referral to our facility.
There were no previous hospital admissions or blood transfusions. Genotype is unknown. However, there was no history suggestive of sickle cell anaemia. She is a product of term gestation delivered to a 27-year-old primiparous woman who registered for ANC at 6 months gestation. She had routine medications in pregnancy. Delivery was through elective caesarean section on account of abnormal lie at term. Birth weight was 4.2 kg and postnatal period was uneventful.
She was fed with breast milk and formula milk for 6 months after which she was introduced to maize gruel fortified with infant formula. She is currently on adult diet and mother emphasised that she feeds very frequently, about 6–8 times/day. There was no delay in developmental milestones. She is the only child in a monogamous, non-consanguineous family setting. There was no family history of similar presentation.
On examination, she was small for age, with the fluffy and sparse scalp hair, afebrile, not pale, anicteric, not dehydrated and no significant peripheral lymphadenopathy. Her weight was 7 kg and length was 74 cm, these were the 3rd and 15th centile of the World Health Organisation growth chart, respectively. There was no pedal oedema, cyanosis or finger clubbing. The abdomen was uniformly distended, the liver was 12 cm palpable below the right coastal margin, along the mid-clavicular line, firm with smooth surface and liver span was 16 cm along the mid-clavicular line. The spleen was not palpably enlarged, kidneys were not ballot-able, and there was no demonstrable ascites. Abdominal girth was 56 cm. Breath sound was vesicular and normal first and second heart sounds were heard on auscultation, no murmur.
The child was to be admitted and investigated for causes of hepatomegaly with associated undernutrition. However, mother declined admission but represented 17 days later with worsening abdominal swelling, difficulty with breathing, fever and features of respiratory distress. On examination, she was not pale and afebrile. However, she was tachypnoeic, tachycardic and breath sound was bronchovesicular. The child was admitted with a working diagnosis of septicaemia. Investigations revealed packed cell volume of 35%, platelet count of 292,000/mm3, white blood cell count of 14,400/mm3 with neutrophil differential of 25% and lymphocyte-75%. The blood and urine cultures yielded growth of Staphylococcus aureus and klebsiella aerogenes, respectively. Erythrocyte sedimentation rate was elevated to 41 mm/h, while serum total protein and albumin were within the normal limit. Retroviral, hepatitis B surface antigen, hepatitis C and tissue transglutaminase screening were all negative. Electrolyte, urea, creatinine and random blood sugar were essentially normal, whereas the liver transaminases, gamma-glutamyl transferase and serum cholesterol level were elevated. The patient was commenced on intravenous antibiotics and by 48 h, fever subsided and dyspnoea had resolved. On account of raised transaminases and hypercholesterolaemia, further evaluation showed elevated serum uric acid, creatine kinase (CK), low fasting blood sugar of 35 mg/dL and a 2-h postprandial blood glucose of 124 mg/dL.
These findings were suggestive of GSD and the child was scheduled for the extended metabolic screen by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and liver biopsy. Results of HPLC-MS were unremarkable. However, the histology of biopsied liver tissue was highly suggestive of GSD. It revealed a core of liver tissue with the partially disturbed lobular architecture. Portal tracts showed expansion by fibrosis with fibrous septa formation and occasional porto-portal bridging. Bile duct injury were evident. Liver parenchyma showed swollen hepatocytes with sharp borders, compressing sinusoids with centrally and eccentrically located nuclei, rarified cytoplasm and plant-like appearance [Figure 2]. The child was commenced on corn starch feeds every 2–3 h, both during the day and at night. Parents were counselled on avoidance of refined sugar in child diet and the use of soy-based milk. The child was also prescribed minerals and vitamins supplements.
|Figure 2: Photomicrograph of liver biopsy tissue showing swollen hepatocytes with sharp borders, compressing sinusoids with centrally and eccentrically located nuclei, rarified cytoplasm and plant-like appearance (×20)|
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At the follow-up clinic, when child was 36 months old, the child general appearance had improved, her weight was 15.1 kg (50th percentile), height was 97 cm (25th percentile), serum uric acid was normal, hepatomegaly had regressed to 7 cm with liver span of 13 cm and abdominal girth of 51.5 cm, while elevated alanine and gamma-glutamyl transaminases were also regressing [Table 1]. However, the level of aspartate transaminase (AST) and CK remained elevated. Electrocardiographic evaluation was essentially normal. The mother was advised to continue with the raw corn starch and to increase child protein intake. She is doing well on this regimen and now 36 months old. She is being followed up at the out-patient clinic every 12 weeks [Figure 3].
| Discussion|| |
The diagnosis of inborn errors of metabolism presents a challenge to health workers in low-resource settings due to various reasons such as the resemblance of its clinical presentation to common disorders in the tropics and subtropics and non-availability of material and financial resources to confirm its diagnosis. Therefore, it is likely that many cases of GSD and other inborn errors of metabolism are underdiagnosed or misdiagnosed and this could account for lack of reported case of GSD in our environment which underscore the importance of this current case report.
From a metabolic perspective, the combination of marked hepatomegaly, fasting hypoglycaemia, raised uric acid and glycogen accumulation on liver biopsy as seen in our patient is certainly highly suggestive of glycogen storage disease. At the age of 14 months, this could be Type I or Type III GSD. The degree of hepatomegaly would suggest Type 1 more, but these patients present a bit earlier between the age of 6–9 months. In similarity with cases of GSD reported from Inuit, Canada, our patient presented with marked hepatomegaly and increased appetite which likely represent recurrent hypoglycaemia. The key difference between Type I and Type III GSD is in fasting tolerance. Type I GSD would be expected to have a fasting tolerance of no more than 3–4 h, whereas Type III GSD would be expected to maintain glycaemic control for at least 4–6 h., Although fasting tolerance was not done in our patient, the 2-h postprandial blood glucose of 124 mg/dl suggest that fasting tolerance will be longer than 3–4 h. Fasting tolerance is best assessed by giving the child a full bolus feed or meal and then taking glucose and lactate samples serially every 30 min. GSD Type 1 would also be expected to produce lactic acidosis when hypoglycaemic, but with GSD Type III this may not be so apparent.,
Our patient presented repeatedly with associated bacterial sepsis evident by leucocytosis and positive blood culture. Although her percentage neutrophil count was low, it was not in the range of neutropenia typically seen in children with GSD Type Ib. In general, children with inborn errors of metabolism are prone to infections because the accumulated metabolic products may serve as substrate for pathogens to thrive.
In addition, our patient had marginally elevated uric acid level and markedly elevated CK. Unlike GSD Type IIIa, the other GSD types (Type II, IV and V) presenting with elevated CK either do not involve the liver or lack liver symptoms. Therefore, based on the clinical presentation of elevated CK, liver symptoms and liver biopsy findings, this case report clearly fit the diagnosis of GSD Type IIIa.
Currently, genetic testing is usually the first-line diagnostic investigation and most patients get a confirmed diagnosis of GSD and even the type from this investigation. However, this is not possible in low resource settings due to non-availability of equipment and the inability to afford the cost of genetic test on the part of patients. Even in developed countries with all financial capabilities, genetic testing is usually available only at dedicated centres.
When treating children with GSD, the priority is to establish safe fasting tolerance and based on this, give small frequent feeds to prevent recurrent hypoglycaemia. In all types of GSD, it is advisable to avoid refined sugars in their diet because the excess glucose will be converted and stored as glycogen which cannot be utilised when needed. Rather, complex carbohydrate or feeds with high fibre is preferred because of their slow rate of release of glucose. Our patient was commenced on raw corn starch which was well-tolerated. The clinical evidence of well-controlled blood glucose level in our patient was improvement in her nutritional status and regressing hepatomegaly.
It is important to note that the serum levels of AST and CK were increasing in this patient. This is due to the involvement of skeletal muscles in GSD Type IIIa and therefore, deposition of glycogen in myocytes. With increasing age and increasing physical activity of the child, there is the possibility of muscle tissue been easily damaged leading to elevated serum CK and AST. It has been advocated that high intake of protein-rich diet helps with reduction in glycogen deposit in muscles and stabilisation of skeletal muscles. Our patient was advised to take protein rich diet in addition to corn starch. We hope this will lead to drop in serum CK and AST levels and a corresponding improvement in skeletal muscle function.
It is known that fasting tolerance to hypoglycaemia improves with age and most of the time hepatomegaly regresses in children with GSD Type III. However, about 20% of these patients develop significant complications such as chronic fibrosis leading to overt cirrhosis and end-stage liver disease. These complications occur as a result of long-term excessive deposit of glycogen in the liver.
In conclusion, GSD should be suspected in children with unexplained hepatomegaly and investigated accordingly. Important biochemical test that provides clue to diagnosis includes fasting blood sugar, lipid profile and serum uric acid. Management of the child should be aimed at reducing recurrent hypoglycaemia and preventing excessive accumulation of glycogen in the liver and other organs.
We would like to acknowledge Prof. Kelly Deirdre and Dr. Saikat Santra of Birmingham Children's Hospital, United Kingdom for their advice and guide in the management of this patient.
Written informed consent was obtained from the parents of this patient.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]