The profession of genetic counseling (also called genetic counselling in many countries) began nearly 50 years ago in the United States, and has grown internationally in the past 30 years. While there have been many papers describing the profession of genetic counseling in individual countries or regions, data remains incomplete and has been published in diverse journals with limited access. As a result of the 2016 Transnational Alliance of Genetic Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of Genetic Counselling in the UK, we endeavor to describe as fully as possible the global state of genetic counseling as a profession. We estimate that in 2018 there are nearly 7000 genetic counselors with the profession established or developing in no less than 28 countries.

BackgroundMucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives.ResultsThe mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists’ evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs*44, p.Q121*, p.L209Wfs*4, p.T409R, and c.1461_1462insN[710].ConclusionThe age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients.

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Newborn bloodspot screening (NBS) began as a research project in the Philippines in 1996 and was mandated by law in 2004. The program initially included screening for five conditions, with a sixth added in 2012. As screening technology and medical knowledge have advanced, NBS programs in countries with developed economies have also expanded, not only in the number of newborns screened but also in the number of conditions included in the screening. Various approaches have been taken regarding selection of conditions to be screened. With limited resources, low- and middle-income countries face significant challenges in selecting conditions for screening and in implementing sustainable screening programs. Building on expansion experiences in the U.S. and data from California on Filipinos born and screened there, the Philippine NBS program has recently completed its expansion to include 29 screening conditions. This report focuses on those conditions detectable through tandem mass spectrometry. Expanded screening was implemented in a stepwise fashion across the seven newborn screening laboratories in the Philippines. A university-based biochemical genetics laboratory provides confirmatory testing. Follow-up care for confirmed cases is monitored and provided through the NBS continuity clinics across the archipelago. Pre-COVID-19 pandemic, the coverage was 91.6% but dropped to 80.4% by the end of 2020 due to closure of borders between cities, provinces, and islands.

Gaucher disease (GD) is a lysosomal storage disorder caused by the deficiency of the β-glucocerebrosidase enzyme due to disease causing mutations in the GBA1 (glucosidase beta acid) gene, leading to the abnormal accumulation of the lipid glucocerebroside in lysosomal macrophages. This is a review of the clinical features and molecular profiles of 14 Filipino patients with GD. Five patients presented with type 1 disease, two had type 2 GD and seven had type 3 GD. The age of onset for all types was between 1 and 2 years of age but there was a delay of 2.2 years from the time of symptom onset to confirmation of diagnosis. Hepatosplenomegaly, anemia and thrombocytopenia were present in most of the patients. Stunting was seen in 64.3% and bone abnormalities were present in 63.6%. The most common mutant allele detected in this cohort was L483P (previously L444P), followed by F252I, P358A and G241R. IVS2+1 G>A, N409S and G416S mutations were reported singularly. There were 3 patients who were found to have N131S mutations and one patient with D257V mutation, mutant alleles that have only been reported among the Filipinos to date. Except for N409S, the mutations found in this cohort were generally severe and were congruent with the severe phenotypes found in most patients. Of the 14 patients, only 6 were able to undergo enzyme replacement therapy which significantly improved the hematologic parameters and decreased the sizes of the liver and spleen but did not consistently improve the growth and skeletal abnormalities nor alleviate the neurological manifestations of our patients with GD. Improved monitoring through recommended modalities for assessments and tools for evaluation should be implemented in order to fully appreciate the severity of the disease and accuracy of the response to treatment.

We report a case of a 1-year and 2-month-old girl with clinical features consistent with congenital hemidysplasia with ichthyosis and limb defects syndrome. Sterol analysis from skin flakes revealed increased levels of a mono 4-alpha methyl sterol also seen in plasma as well as the presence of 4-alpha-carboxy-4-methyl-cholest-8(9)-en-3beta-ol and several keto-sterols, which are usually below the limit of detection. This sterol pattern is consistent with abnormal function of the 4-alpha-methylsterol-4-demethylase complex. NSDHL gene testing revealed the presence of a variant of uncertain significance, c.130G>A (p.Gly44Ser). This missense mutation currently is not included in population databases (ExAC no frequency) and has not been reported in individuals with an NSDHL-related condition. Parental studies showed that neither parent carries the NSDHL variant. On this basis, this variant has been reclassified as likely pathogenic. Symptomatic treatment with keratolytic agents, emollients and ketoconazole was initiated.

Maple syrup urine disease (MSUD, MIM # 248600 ) is an autosomal recessive metabolic disorder that results in elevation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Elevation of BCAA and certain alpha keto-acids is associated with a catabolic state and may result in neurological and developmental delays, feeding problems, and a urine and cerumen odor of maple syrup. Pregnancy is a period of multiple adaptations necessary to support fetal growth and development. Both the third trimester of pregnancy and the postpartum period present the possibility for catabolic states. We describe our treatment of an adolescent patient with intermittent MSUD and her resulting positive pregnancy outcome.

Schinzel-Giedion syndrome is a rare condition characterized by dysmorphic features, neurologic features, urogenital abnormalities, and radiographic changes. The etiology has been traced to mutations in the SETBP1 gene. We report a Filipino patient with features suggestive of Schinzel-Giedion Syndrome and the first to be confirmed through molecular testing.