Friday, October 14, 2011

A rare disease...

The neurologist called me after I blogged the other day to tell me that she had spoken with the genetic and metabolic specialist at Texas Children’s Hospital and that they suspect Jacob has a rare disease called creatine synthesis disorder AGAT.  His blood work showed that he was low in the amino acid arginine.  To date there have only been 7 reported occurrences of this disease in the world.  This disease can cause autism, self mutilation, mental retardation, severe language delays, epilepsy and heart failure.  It is treatable; however, the treatment has to be carefully monitored as it can cause renal failure.  We are going to Texas Children’s to do more testing to be sure that he has this disease.  From what I have researched, there is a chance that the treatment can improve Jacob’s intellectual delays.  The unfortunate thing is that while it may improve his autistic symptoms, it’s an extremely dangerous disease.  Please be in prayer for Jacob.  If you want more info I copied and pasted info below on the disease:

I got this information off the web page

Disease characteristics. The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT or GATM) deficiency, and the creatine transporter (SLC6A8) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; a significant proportion have pyramidal/extrapyramidal findings. Onset is between ages three months and three years. Only seven individuals with AGAT deficiency have been reported. The phenotype of SLC6A8 deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, and behavior disorder; age at diagnosis ranges from two to 66 years. Females heterozygous for SLC6A8 deficiency may have learning and behavior problems.
Diagnosis/testing. Cerebral creatine deficiency in cranial MR spectroscopy (MRS) is the characteristic hallmark of all CCDS. Diagnosis of CCDS relies on: measurement of guanidinoacetate (GAA), creatine, and creatinine in urine and plasma; and molecular genetic testing of the three genes involved, GAMT, GATM, or SLC6A8. If molecular genetic test results are inconclusive, GAMT enzyme activity (in cultured fibroblast or lymphoblasts), GATM enzyme activity (in lymphoblasts), or creatine uptake in cultured fibroblasts can be assessed.
Management. Treatment of manifestations: GAMT deficiency and AGAT deficiency are treated with oral creatine monohydrate to increase cerebral creatine levels. Treatment of GAMT deficiency may also require supplementation of ornithine and dietary restriction of arginine. In males with SLC6A8 deficiency creatine supplementation alone does not improve clinical outcome and does not result in increased cerebral creatine levels; likewise, high-dose L-arginine and L-glycine supplementation did not improve clinical or biochemical outcome. One female with intractable epilepsy responded to high-dose L-arginine and L-glycine supplementation with cessation of seizures.
Prevention of primary manifestations: Whether early treatment prevents disease manifestations is unknown; however, newborn sibs of individuals with AGAT or GAMT deficiency seem to benefit from early treatment.
Surveillance: In those treated with creatine monohydrate, routine measurement of renal function to detect possible creatine-associated nephropathy is warranted.

AGAT (GATM) Deficiency

To date seven individuals from three families have been diagnosed with AGAT deficiency [Item et al 2001, Battini et al 2002, Battini et al 2006, Johnston et al 2005, Edvardson et al 2010].
In one extended Italian family, two sisters had global developmental delay; one had occasional fever-induced seizures [Item et al 2001]. Their younger sib, diagnosed at age three weeks and treated with creatine supplementation starting at age four months, was reported to have normal development at age 18 months [Battini et al 2006]. A second cousin of the three sibs who presented with global developmental delay was also affected [Battini et al 2002].
In the second family, a 14-month old American girl of Chinese descent presented with psychomotor delay, severe language impairment, failure to thrive, and autistic behavior [Johnston et al 2005].
In the third family, two siblings, age 21 years and 14 years, presented with mild intellectual disability, muscle weakness, and failure to thrive at age two years. Both had the novel features of proximal muscle weakness and fatigability [Edvardson et al 2010].

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