GSD1 Subtype 1B: Timeline and progression of clinical symptoms in a patient with juvenile idiopathic arthritis.
Biochemical/Metabolic and Therapeutics
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Introduction
Glycogen storage disease type 1 is an inherited disorder of glycogen metabolism characterized by fasting hypoglycemia, increased lactate, hepatomegaly, hyperuricemia, hypertriglyceridemia and enlarged kidneys. It is comprised of 2 major subtypes, GSD Ia and GSD Ib. GSD1a is due to deficiency of glucose 6 phosphatase activity while GSD 1b exhibits normal G6Pase enzyme activity but a deficiency of the transporter enzyme, glucose-6-phosphate translocase (G6PT).
Case Presentation
We report an 11-year-old girl with GSD1b who presented at 7 months of age with vomiting, altered mental status after overnight fasting. Her initial clinical examination findings of small length, full cheeks, and hepatomegaly along with biochemical results of severe hypoglycemia, lactic acidosis, hypertriglyceridemia were pathognomonic for GSD type 1.
Diagnostic Workup
Molecular testing identified a heterozygous pathogenic variant in exon 9 c.1042_1043delCT in SLC37A4 gene causing premature protein termination and a heterozygous pathogenic variant Exon 1–3deletion in the SCL37A4 gene.
Treatment and Management
She was managed on corn starch every 4 h until 2 years of age. At age of 2, she started with long-acting maize-based starch at bedtime to improve sleep. She had recurrent bacterial infections: gingivitis, mastoiditis, and recurrent oral ulcers, each of which required hospital admission for antibiotics and GCSF. She also required admissions for management of hypoglycemia. She contracted MISC-COVID in 2020, requiring GCSF, intravenous immunoglobulin, and packed red blood cells to treat anemia. At age 7, she was started on SGLT-2 inhibitor and has been on it for almost 3 years. This intervention significantly improved her neutrophil counts and her need for inpatient admissions. After almost 2 years on SGLT-2 inhibitor, she became ill with symptoms of rash, vomiting, arthritis, diarrhea, and markedly increased ferritin levels. Ultimately, she was diagnosed with systemic Juvenile Idiopathic Arthritis(JIA). She is currently very well controlled on two biologics (tofacitinib and tocilizumab) after failing numerous other treatments.
Outcome and Follow-Up
Despite her extensive complicated course of illness, she continues to grow well with appropriate developmental milestones. Her ultrasounds show stable hepatomegaly and mildly enlarged kidneys. She had her menarche at age 10-11 years, maintaining her platelet levels. Her absolute neutrophil count (ANC) is well controlled on SGLT-2 inhibitor, and her JIA has been in remission for more than a year. Her JIA flares are also in control at present.
Discussion
GSD-1b is known to be associated with neutrophil dysfunction and autoimmune disease. Systemic JIA is a disease caused by problems in innate immunity with neutrophil and monocyte/macrophage dysfunction. No case of GSD-1b associated with systemic JIA has been reported. Our patient was doing well on SGLT2 inhibitor which significantly improved her neutropenia, and reduced the infection frequency, but after 2 years of treatment, developed JIA, which from our understanding can be an association with the disease itself rather than the medication.
Conclusion
We describe an 11-year-old girl diagnosed with GSD1b in infancy and a timeline of her clinical symptoms and management along with rheumatological disease, which could be a result of inflammatory dysfunction.
Glycogen storage disease type 1 is an inherited disorder of glycogen metabolism characterized by fasting hypoglycemia, increased lactate, hepatomegaly, hyperuricemia, hypertriglyceridemia and enlarged kidneys. It is comprised of 2 major subtypes, GSD Ia and GSD Ib. GSD1a is due to deficiency of glucose 6 phosphatase activity while GSD 1b exhibits normal G6Pase enzyme activity but a deficiency of the transporter enzyme, glucose-6-phosphate translocase (G6PT).
Case Presentation
We report an 11-year-old girl with GSD1b who presented at 7 months of age with vomiting, altered mental status after overnight fasting. Her initial clinical examination findings of small length, full cheeks, and hepatomegaly along with biochemical results of severe hypoglycemia, lactic acidosis, hypertriglyceridemia were pathognomonic for GSD type 1.
Diagnostic Workup
Molecular testing identified a heterozygous pathogenic variant in exon 9 c.1042_1043delCT in SLC37A4 gene causing premature protein termination and a heterozygous pathogenic variant Exon 1–3deletion in the SCL37A4 gene.
Treatment and Management
She was managed on corn starch every 4 h until 2 years of age. At age of 2, she started with long-acting maize-based starch at bedtime to improve sleep. She had recurrent bacterial infections: gingivitis, mastoiditis, and recurrent oral ulcers, each of which required hospital admission for antibiotics and GCSF. She also required admissions for management of hypoglycemia. She contracted MISC-COVID in 2020, requiring GCSF, intravenous immunoglobulin, and packed red blood cells to treat anemia. At age 7, she was started on SGLT-2 inhibitor and has been on it for almost 3 years. This intervention significantly improved her neutrophil counts and her need for inpatient admissions. After almost 2 years on SGLT-2 inhibitor, she became ill with symptoms of rash, vomiting, arthritis, diarrhea, and markedly increased ferritin levels. Ultimately, she was diagnosed with systemic Juvenile Idiopathic Arthritis(JIA). She is currently very well controlled on two biologics (tofacitinib and tocilizumab) after failing numerous other treatments.
Outcome and Follow-Up
Despite her extensive complicated course of illness, she continues to grow well with appropriate developmental milestones. Her ultrasounds show stable hepatomegaly and mildly enlarged kidneys. She had her menarche at age 10-11 years, maintaining her platelet levels. Her absolute neutrophil count (ANC) is well controlled on SGLT-2 inhibitor, and her JIA has been in remission for more than a year. Her JIA flares are also in control at present.
Discussion
GSD-1b is known to be associated with neutrophil dysfunction and autoimmune disease. Systemic JIA is a disease caused by problems in innate immunity with neutrophil and monocyte/macrophage dysfunction. No case of GSD-1b associated with systemic JIA has been reported. Our patient was doing well on SGLT2 inhibitor which significantly improved her neutropenia, and reduced the infection frequency, but after 2 years of treatment, developed JIA, which from our understanding can be an association with the disease itself rather than the medication.
Conclusion
We describe an 11-year-old girl diagnosed with GSD1b in infancy and a timeline of her clinical symptoms and management along with rheumatological disease, which could be a result of inflammatory dysfunction.