Glycogen storage disease type VI with a novel PYGL mutation

Abstract

Rationale: Glycogen storage disease (GSD) type VI is a rare disease caused by the inherited deficiency of liver phosphorylase. Patient concerns: The proband, a 61-month-old Chinese boy, manifested intermittent hematochezia, growth retardation, hepatomegaly, damage of liver function, mild hypoglycemia, and hyperlactatemia. The other patient was a 107-month-old Chinese girl with growth retardation, hepatomegaly, mild hypoglycemia, and hyperlactatemia. In order to further confirm the diagnosis, we conducted a liver biopsy and detected blood samples for their gene using IDT exon chip capture and high-throughput sequencing. Diagnoses: According to the clinical symptoms, physical examination, laboratory examinations, liver biopsy, and the genetic test finding, the 2 patients were diagnosed GSD VI. Interventions: They were treated mainly with uncooked cornstarch. Outcomes: There were 2 mutations of PYGL gene in this pedigree. c.2467C>T (p. Q823X) and c.2178-2A>C occurred both in the proband and his second sister. Lessons: As a novel mutation, c.2178-2A>C enriches the mutation spectrum of PYGL gene. The different degrees of elevated lactate is an unusual phenotype in GSD VI patients. It is not clear if this is caused by the new mutation of c. 2178-2A > C. Long-term complications remains to be observed.

The Phenotypic and Genetic Spectrum of Glycogen Storage Disease Type VI

“…Apart from liver-specific complications, other long-term complications were rare. In one patient, academic achievement was reported to be below average [7], but no other neurologic complications were observed. No patient developed symptomatic cardiomyopathy, but in one child, an increase in septum wall thickening (z-score: −3.2) and left ventricular posterior wall thickening was reported at the age of 4 years and 3 months [15].…”

“…GSD VI is usually considered a relatively mild disorder [1]; however, more severe cases with recurrent hypoglycemia, liver cirrhosis or developmental delay have been reported [6][7][8]. Phenotypic information on GSD VI is currently only available from published case reports and small case series.…”

“…Especially, long-term outcome data on patients with GSD VI are scarce. Published findings suggest significant clinical heterogeneity, and although GSD VI is usually considered a relatively mild disorder [1], some severe cases with recurrent hypoglycemia, liver cirrhosis or developmental delay have been described [6][7][8].…”

Glycogen storage diseases with liver involvement: a literature review of GSD type 0, IV, VI, IX and XI

“…In GSD type IV the accumulation of abnormal glycogen, less soluble than normal glycogen, causes a foreign body reaction with consequent osmotic swelling and cell death [ 50 ], leading to interstitial fibrosis evolving toward cirrhosis [ 24 ]. Liver fibrosis is outlined also in individuals with GSD types VI [ 38 , 66 ] and IX [ 4 , 51 ]. Particularly, in GSD type IX fibrosis has been recently reported to range between 33 and 95% depending on the subtype still in early infancy [ 4 ].…”

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

“…GSD VI is rare relative to other types of GSD, with an incidence of 1/60,000 to 1/85,000 ( Zhan et al, 2021 ). As the only causative gene of GSD VI, PYGL gene has been recorded 80 types of mutations in the HGMD database (22 April 2022), among which missense/nonsense mutations are the most common.…”